title: Simple catalytic mechanism for the direct coupling of α-carbonyls with functionalized amines: a one-step synthesis of Plavix.
abstract: The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone.
authors.affiliation: Merck Center for Catalysis at Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Evans
authors.forename: Jason R
authors.initials: JR
authors.lastname: Zbieg
authors.forename: Shaolin
authors.initials: S
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: David W C
authors.initials: DW
authors.lastname: MacMillan
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry; D002384:Catalysis; D000077144:Clopidogrel; D003300:Copper / Q000737:chemistry; D004053:Diethylpropion / Q000138:chemical synthesis; D004952:Esters / Q000737:chemistry; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D000447:Aldehydes; D000588:Amines; D001965:Bromides; D004952:Esters; D003300:Copper; D000077144:Clopidogrel; D013988:Ticlopidine; D004053:Diethylpropion